Randomized controlled trial investigating the efficacy of oral azithromycin in preventing perinatal infections in pregnant women undergoing labor induction

Abstract Objectives This study evaluates oral azithromycin's effectiveness in reducing intrapartum and puerperal infection rates in term pregnant women undergoing labor induction to guide antibiotic prophylaxis. Methods This single‐center randomized controlled trial enrolled 472 women with term singleton pregnancies undergoing labor induction. The participants were randomly allocated to receive either 2 g of oral azithromycin ( n = 236) or no treatment ( n = 236). The primary outcome was the overall perinatal infection rate (which includes both intrapartum and/or puerperal infections). Secondary outcomes included maternal and neonatal complications, mode of delivery, and safety parameters. Results analysis adopted an intention‐to‐treat approach. Results The overall perinatal infection rate did not differ significantly between the azithromycin group (16.1%) and the control group (16.9%) (absolute risk difference [ARD] = −0.85%, relative risk [RR] = 0.950, 95% confidence interval 0.633–1.425; P = 0.804). Similarly, the incidence of neonatal infectious diseases showed no significant difference between the two groups (2.5% vs 5.1%, P = 0.149). Both groups had comparable outcomes in mode of delivery, maternal–neonatal complications (epidural analgesia, postpartum hemorrhage, and pre‐ and post‐delivery antibiotic use), total labor duration, neonatal hypoglycemia, neonatal intensive care unit admission, and neonatal antibiotic administration. Maternal outcomes did not differ significantly between groups, although 3.4% (8/236) of women in the azithromycin group reported gastrointestinal symptoms during labor, with a total adverse event rate of 3.8% (9/236, including one case of dizziness). Conclusion The use of an additional 2 g azithromycin provides no additional benefit in reducing the overall risk of maternal infection and perinatal infection in an already intensive antibiotic prophylactic and well‐resourced setting. Clinical Trial Registration This study was registered in the Chinese Clinical Trial Registry, registration number ChiCTR2300077629, November 14, 2023 ( https://www.chictr.org.cn/showprojEN.html ).